Regulation of mRNP dynamics in gene expression:
Eukaryotic gene expression is a fundamental cellular activity that is critical for cellular identity, function, and physiology. During gene expression, a messenger RNA (mRNA) is generated by transcription and undergoes a number of different steps, including splicing and nuclear processing, nucleocytoplasmic export and localization, translation, and decay. These steps result in dynamic changes to the RNA sequence, structure, and the cohort of proteins bound to the mRNA. Furthermore, these changes need to occur with the proper timing and in the correct sequence to avoid aberrant expression. Therefore elaborate regulation of mRNP dynamics is required for proper gene expression. At virtually every step in gene expression, members of a highly conserved protein family called the DEAD-box proteins are required for facilitating mRNP transitions by acting either as RNA helicases or as ribonucleoprotein (RNP) remodeling enzymes. Furthermore, by regulating their activity, the potential exists to control mRNAs in different subsets and in response to different conditions. Thus we hypothesize that the DEAD-box proteins exert overarching control of mRNP dynamics in gene expression.
Our research in the Bolger lab has dual goals: 1. addressing fundamental biological questions, and 2. utilizing this knowledge to advance human health. The Bolger laboratory uses the budding yeast Saccharomyces cerevisiae as a model system, and takes advantage of the combination of genetics, biochemistry, and cell biology allowed by yeast work. Our long-term goal in fundamental biology is to uncover the regulation of mRNP dynamics. Specifically, we are focusing on the in vivo roles, molecular targets, and regulation of DEAD-box proteins. Our research will not only greatly increase our understanding of how these factors function in the control of gene expression but also may open up new avenues for therapies, either for cancer or for the other pathologies related to this research.